The principal focus of this research proposal is to test the hypothesis that a unique liposome-associated HSV2 antigen delivery system will induce protective T cell and/or B cell immune responses in mice following systemic or mucosal vaccination. The vaccine to be used in these studies is comprised of an HSV2 protein epitope from either the gD or gB viral envelope proteins fused to a hydrophobic domain to promote stable association of the epitope with the liposomal membranes. It is hypothesized that liposomes will play a critical role in antigen delivery because liposomes accumulate in the phagocytic cells of the body whether they are administered systematically or mucosally. The Specific Aims are: 1) To optimize the dosing regimen with liposome-based gD or gB antigen vaccines, given systematically or mucosally, to produce protective B and T cell responses against vaginal HSV2 challenge of BALB/c and C57BL/6 mice; 2) To characterize the T cell and B cell immune responses produced in BALB/c and C57BL/6 mice; 2) To characterize the T cell and B cell immune responses produced in BALB/c and C57BL/6 mice treated systemically or mucosally with the protective vaccines by using splenic T cells to assay for cytolytic activity and cytokine production and serum and mucosal secretions to screen for antibody isotopes and neutralizing antibodies; 3) To test whether co- administration of selected cytokine(s) with the antigen-liposome vaccine will enhance the protective immune response to the vaccine; and 4) To determine if the therapeutic treatment of mouse intravaginal HSV2 infection can be improved if the antigen-liposome vaccine were used with antiviral drugs, such as Aciclovir, to provide infected animals with both immunotherapy and chemotherapy. A better understanding of the immune responses elicited by this type of vaccine, when administered systematically or mucosally to BALB/c or C57BL/6 mice, will help to improve our understanding of how to produce effective vaccines for the treatment of HSV2 and other genitally transmitted virus infections.